8-30836859-G-C

Position:

• chr8-30836859-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001350162.2(TEX15):​c.9425C>G​(p.Ala3142Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEX15 NM_001350162.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19

Genes affected

TEX15 (HGNC:11738): (testis expressed 15, meiosis and synapsis associated) This gene encodes a protein that is required for DNA double-strand break repair, chromosome synapsis, and meiotic recombination in spermatocytes. Male mice with a knockout of the orthologous gene are viable but sterile. Loss-of-function mutations in the orthologous mouse gene cause early meiotic arrest in spermatocytes, before the mid-pachytene stage. Naturally occurring mutations in this gene are associated with nonobstructive azoospermia. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX15	NM_001350162.2	c.9425C>G	p.Ala3142Gly	missense_variant	10/11	ENST00000643185.2	NP_001337091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX15	ENST00000643185.2	c.9425C>G	p.Ala3142Gly	missense_variant	10/11		NM_001350162.2	ENSP00000493555	P4
TEX15	ENST00000256246.5	c.8276C>G	p.Ala2759Gly	missense_variant	3/4	1		ENSP00000256246
TEX15	ENST00000638951.1	c.9437C>G	p.Ala3146Gly	missense_variant	9/10	5		ENSP00000492713	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 26, 2023

The c.8276C>G (p.A2759G) alteration is located in exon 3 (coding exon 3) of the TEX15 gene. This alteration results from a C to G substitution at nucleotide position 8276, causing the alanine (A) at amino acid position 2759 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;T;.
Eigen	Benign	-0.0095
Eigen_PC	Benign	-0.080
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.092	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.1	.;N;.
REVEL	Benign	0.092
Sift	Uncertain	0.029	.;D;.
Sift4G	Uncertain	0.019	.;D;.
Polyphen		0.93	.;P;.
Vest4		0.21
MutPred		0.12		.;Gain of catalytic residue at P2755 (P = 0.0678);.;
MVP		0.29
MPC		0.038
ClinPred		0.58	D
GERP RS		4.7
Varity_R		0.13
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.26		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-30694375;